Background/Rationale: The use of opioid medications to treat chronic pain has rapidly increased. However, opioids are associated with significant harms, including medical adverse effects, misuse, abuse, and diversion. Unfortunately, there are currently no evidence-based treatments available to reduce prescription opioid abuse or other adverse effects in the primary care setting. Objectives: The objectives of this study are to: (a) evaluate whether a multifaceted intervention (Improving the Safety of Opioid Prescribing; ISOP) enhances opioid safety, (b) assess to what extent assignment to ISOP impacts processes of care, and (c) explore to what extent ISOP is associated with changes in pain intensity, function, quality of life, and depressive symptoms. Methods: To achieve these objectives, we propose a randomized controlled trial to test the efficacy of a multifaceted patient-centered intervention to improve opioid safety. We will randomize primary care providers (PCPs) and their associated PACT nurse (n=64 of each); patients (n=320) will be nested by clinician status. PCPs and PACT nurses will participate in either an educational workshop versus workshop plus intervention. An intervention nurse care manager will maintain a registry of enrolled patients, track clinical progress and care provided through the electronic medical record, track urine drug test administrations and results, monitor state Prescription Drug Monitoring Program data, and collaborate with an internist and substance abuse specialist to provide decision support to PCPs when patients demonstrate evidence of prescription opioid misuse or abuse. Decision support will specifically address best practices for modifying treatment when patients misuse or abuse prescription opioids and for communicating with patients about treatment options and decisions. The nurse care manager will also meet individually with enrolled participants to discuss strategies for preventing/reducin opioid adverse effects, preventing diversion, and providing rationale for screening for prescription opioid abuse. The intervention will focus on reducing prescription opioid abuse and adverse effects of opioids, while also working to improve quality of the clinician-patient relationship. Anticipated Impacts on Veteran's Healthcare: Opioid medications are commonly prescribed for veterans with chronic pain. Unfortunately, these medications are also associated with significant adverse effects, including prescription opioid misuse, abuse, and diversion. If th results from this study are significant, this will provide a pragmatic intervention to assist primay care providers in reducing prescription opioid abuse and other adverse effects, and improving patient's satisfaction with care.